Follow-up Survey of Donor Candidates for Living Related Kidney Transplantation With Prostate Cancer.

INTRODUCTION: With the increasing number of elderly kidney donor candidates due to the lack of available donors, prostate cancer has sometimes been detected in these candidates during pretransplant screening examinations. There are currently no guidelines or consensus on prostate cancer screening and treatment in donors. We retrospectively evaluated the clinical course of donor candidates with prostate cancer. METHODS: Between January 2006 and December 2016, 9 donor candidates for living related kidney transplantation were incidentally diagnosed with prostate cancer at our institution. All male kidney transplant donor candidates routinely received prostate-specific antigen (PSA) testing. The patients with PSA levels > 4.0 ng/mL underwent prostate biopsies. For future kidney transplantation, treatment for localized prostate cancer was prostatectomy. RESULTS: Seven low- or intermediate-risk patients according to the D'Amico risk classification underwent endoscopic prostatectomy, while 2 high-risk patients underwent high dose-rate brachytherapy to prioritize prostate cancer treatment. Of the 7 who underwent surgery, 3 patients ultimately became living related kidney transplantation donors for their wives. There was no recurrence of PSA elevation after treatment. CONCLUSION: This study showed that donor candidates with prostate cancer could safely donate a kidney after a thorough evaluation to exclude those with high-risk prostate cancer. Transmission of prostate cancer through kidney transplantation seems unlikely and robot-assisted laparoscopic prostatectomy may be feasible for donor candidates with localized prostate cancer.

Living Related Renal Transplantation Using a Saphenous Vein Graft: A Case Report.

We report a case of living related renal transplantation that used the recipient's saphenous vein as a graft to extend the length of the right donor renal vein. A 41-year-old woman underwent ABO-incompatible living related renal transplantation from her 74-year-old mother in November 2014. A retroperitoneal laparoscopic right donor nephrectomy was performed, because the right kidney showed a cyst on preoperative computed tomography. As the right kidney after donor nephrectomy had a short renal vein and the kidney was large at 280 g, anastomosis with the external iliac vein was difficult. Therefore, we obtained the recipient's 15-cm-long right saphenous vein and created a 1 cm saphenous vein graft. We anastomosed 1 side of the saphenous vein graft to the allograft renal vein in bench surgery and performed end-to-side anastomosis of the other end to the recipient's external iliac vein. The allograft renal artery was used to perform end-to-end anastomosis to the recipient's internal iliac artery. Allograft kidney function was good after transplantation. When the longer axis of the renal graft vein is short, as in the right kidney, a saphenous vein graft may be useful.

Effects of cocoa-enriched diet on orofacial pain in a murine model.

OBJECTIVES: To investigate and discuss the effects of cocoa on orofacial pain. SETTING AND SAMPLE POPULATION: The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested. MATERIALS AND METHODS: Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changing their food from the standard chow to a cocoa-enriched or control-equivalent diet. RESULTS: Male rats fed the cocoa diet had a significantly higher operant pain index when tested at 37°C as compared to control diet-fed animals. Female rats on the cocoa diet had a significantly higher pain index when tested at 18°C and 44°C, as compared to animals fed the control diet. Capsaicin-induced pain was inhibited, with cocoa-diet male rats having a significantly higher pain index than control-diet male rats and cocoa-diet female rats at both 37°C and 44°C. Cocoa-diet female rats had a significantly higher pain index at 44°C than control-diet females. Mechanical sensitivity was affected following capsaicin cream, with a significantly decreased tolerated bottle distance in both cocoa- and control-diet animals, but there was no difference between cocoa- and control-diet groups. CONCLUSION: Using the OPAD operant system, we demonstrated that a diet rich in cocoa was effective in inhibiting neurogenic inflammatory pain in rats. This has implications for the use of novel alternative therapies such as diet modification for pain control.

Preemptive Living Donor Kidney Transplantation and Kidney Function at the Initial Hospital Visit: A Single-Center Case-Control Study.

BACKGROUND: Studies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. METHODS: A single-center, case-control study was conducted to determine the clinical factors that lead to referral for PKT. RESULTS: Between April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT-, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT-, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). CONCLUSIONS: Our results indicate that PKT should be performed within ∼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.

Robot-Assisted Radical Prostatectomy for Localized Prostate Cancer in Asian Renal Transplant Recipients.

BACKGROUND: The purpose of this study was to present our experience with robot-assisted radical prostatectomy (RARP) for localized prostate cancer in renal transplant recipients (RTRs) and to determine the feasibility and efficacy of RARP in these patients. METHODS: We retrospectively reviewed the medical records of 236 patients who underwent RARP for localized prostate cancer at our institution between August 2011 and July 2015 and identified 3 patients who were RTRs. We reviewed the available clinical data of the 3 patients. RESULTS: All patients underwent RARP successfully without any major complications. The mean operation time was 162 minutes (range, 127-195 minutes). The mean estimated blood loss was 52 mL (range, 30-75 mL); therefore, the patients did not need any perioperative blood transfusion. In all cases, graft function, as determined according to the serum creatinine level, was stable during and after the operation. Pathological examination showed negative surgical margins with organ-confined disease in all patients. CONCLUSIONS: We reported 3 RTRs with localized prostate cancer who were treated with RARP. RARP might be a feasible and effective minimally invasive technique for the treatment of localized prostate cancer in carefully selected RTRs.

ABO-Incompatible Living Kidney Transplants: Evolution of Outcomes and Immunosuppressive Management.

ABO-incompatible living kidney transplantation (ABO-ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO-ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO-ILKT compared with those from ABO-compatible living kidney transplantation (ABO-CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032-including 247 ABO-ILKT and 785 ABO-CLKT cases-were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO-compatibility. In the past decade, ABO-ILKT and ABO-CLKT recipients yielded almost equivalent outcomes with respect to the 9-year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59-3.22, p = 0.455). The graft survival rate for ABO-ILKT conducted between 2005 and 2013 was better than that for ABO-ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13-0.72, p = 0.007). ABO-ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO-incompatibility. Currently, ABO-ILKT is an acceptable treatment for patients with end-stage renal disease.

Clonal Deletion Established via Invariant NKT Cell Activation and Costimulatory Blockade Requires In Vivo Expansion of Regulatory T Cells.

Recently, the immune-regulating potential of invariant natural killer T (iNKT) cells has attracted considerable attention. We previously reported that a combination treatment with a liposomal ligand for iNKT cells and an anti-CD154 antibody in a sublethally irradiated murine bone marrow transplant (BMT) model resulted in the establishment of mixed hematopoietic chimerism through in vivo expansion of regulatory T cells (Tregs). Herein, we show the lack of alloreactivity of CD8(+) T cells in chimeras and an early expansion of donor-derived dendritic cells (DCs) in the recipient thymi accompanied by a sequential reduction in the donor-reactive Vß-T cell receptor repertoire, suggesting a contribution of clonal deletion in this model. Since thymic expansion of donor DCs and the reduction in the donor-reactive T cell repertoire were precluded with Treg depletion, we presumed that Tregs should preform before the establishment of clonal deletion. In contrast, the mice thymectomized before BMT failed to increase the number of Tregs and to establish CD8(+) T cell tolerance, suggesting the presence of mutual dependence between the thymic donor-DCs and Tregs. These results provide new insights into the regulatory mechanisms that actively promote clonal deletion.

Plasma Cell-Rich Rejection After Kidney Transplantation and the Role of Donor-Specific Antibodies: A Case Report and Review of the Literature.

OBJECTIVE: We report a case of the clinical course and pathologic findings for a kidney transplant recipient with plasma cell-rich rejection (PCRR) accompanied by antibody-mediated rejection (ABMR). METHODS: A 29-year-old man with end-stage renal disease caused by lupus nephritis received an ABO-compatible living kidney transplant. RESULTS: Eighteen months after transplantation, the patient presented with proteinuria and increased serum creatinine. An episode biopsy revealed severe tubulointerstitial infiltration with plasma cells accompanied by peritubular capillaritis and positive findings on immunofluorescent C4d staining. Donor-specific antibodies were positive for DR52, and the patient was subsequently diagnosed with PCRR accompanied by ABMR. Treatment was initiated with high-dose steroids, intravenous immunoglobulin, gusperimus hydrochloride, muronmonab antibody CD3, and rituximab. However, ABMR persisted and allograft failure developed 20 months after onset. CONCLUSIONS: We argue that PCRR accompanied by ABMR is a subtype of PCRR that can progress to allograft failure owing to persistent ABMR.

A novel approach inducing transplant tolerance by activated invariant natural killer T cells with costimulatory blockade.

Invariant natural killer T (iNKT) cells are one of the innate lymphocytes that regulate immunity, although it is still elusive how iNKT cells should be manipulated for transplant tolerance. Here, we describe the potential of a novel approach using a ligand for iNKT cells and suboptimal dosage of antibody for CD40-CD40 ligand (L) blockade as a powerful method for mixed chimerism establishment after allogenic bone marrow transplantation in sublethally irradiated fully allo recipients. Mixed-chimera mice accepted subsequent cardiac allografts in a donor-specific manner. High amounts of type 2 helper T cytokines were detected right after iNKT cell activation, while subsequent interferon-gamma production by NK cells was effectively inhibited by CD40/CD40L blockade. Tolerogenic components, such as CD11c(low) mPDCA1(+) plasmacytoid dendritic cells and activated regulatory T cells (Tregs) expressing CD103, KLRG-1 and PD-1, were subsequently augmented. Those activating Tregs seem to be required for the establishment of chimerism because depletion of the Tregs 1 day before allogenic cell transfer resulted in a chimerism brake. These results collectively suggest that our new protocol makes it possible to induce donor-specific tolerance by enhancement of the innate ability for immune tolerance in place of the conventional immunosuppression.

Clinicopathologic analysis of acute vascular rejection cases after renal transplantation.

INTRODUCTION: Histopathologic change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. PATIENTS: AVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. RESULTS: Among 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2-t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid-resistant rejection (SRR) requiring greater anti-rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. CONCLUSIONS: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression.

Chronic antibody-mediated rejection is reduced by targeting B-cell immunity during an introductory period.

Transplantation across blood group antigen and human leukocyte antigen (HLA) barriers are immunologically high risk. Both splenectomy and rituximab injection were developed to overcome those immunological barriers. The idea behind these treatments is to control B-cell immunity before and after renal transplantation and antibody production. Between January 2001 and December 2004, recipients underwent pretransplant double-filtration plasmapheresis (DFPP) and splenectomy at the time of transplantation in the ABO-incompatible group (ABO-I-SPX; n= 45). From January 2005 to June 2009, a low dose of rituximab was given as an alternative to splenectomy (ABO-I-RIT; n = 57). As a control group, we selected 83 cases of ABO-C living-donor kidney transplantation between January 2001 and December 2007 (ABO-C). We compared the graft survival rate and chronic antibody-mediated rejection (C-AMR) rate between ABO-C and ABO-I kidney transplantation with induction treatment. C-AMR rates 2 years after the operation were 8.8, 3.5 and 28.9%, and de novo donor-specific anti-HLA antibody (DSHA) positive rates were 2.2, 1.7 and 18.1% in the ABO-I-SPX, ABO-I-RIT and ABO-C groups, respectively. The ABO-C group showed the highest rate of C-AMR and de novo DSHA. B-cell depletion protocols, such as splenectomy or rituximab administration, reduced C-AMR after kidney transplantation.

Risk factors for deterioration of renal function after donor nephrectomy.

INTRODUCTION: There are few recent studies investigating increased risks for adverse effects leading to chronic kidney disease (CKD) among kidney donors. The aim of this study was to identify factors that protect renal function among actual live kidney donors. MATERIALS AND METHODS: We enrolled 68 individuals who had undergone donor nephrectomy in this study. We assessed donor age, body mass index (BMI), casual blood pressure, preoperative and 3-month follow-up serum creatinines, serum total cholesterol, and several other clinical parameters. The severity of arteriosclerosis in the arteriolar and interlobular arteries of the donor kidney was semiquantitatively evaluated in 4 grades using back table biopsies. Impairment of renal function after surgery was expressed by differences in serum creatinine levels. RESULTS: The ratio of glomerular sclerosis, systolic blood pressure, and diastolic blood pressure positively correlated with donor age. Deterioration of renal function after donor nephrectomy negatively correlated with BMI and positively correlated with severity of arteriosclerosis in interlobular arteries. A multiple regression analysis model with respect to the severity of arteriosclerosis in interlobular arteries showed significant influence, of serum creatinine and systolic blood pressure. CONCLUSIONS: Preventing progression of arteriosclerosis and selecting the optimal BMI before donor nephrectomy will help to avoid impaired renal function among live kidney donors.

Acute antibody-mediated rejection in living ABO-incompatible kidney transplantation: long-term impact and risk factors.

The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABO-incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long-term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non-AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non-AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti-blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor-specific anti-HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti-blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.

Clinical and histological analysis of chronic tacrolimus nephrotoxicity in renal allografts.

AIM: Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Chronic nephrotoxicity due to TAC has been reported to be similar to that of cyclosporine in kidney transplant patients. Since, the severity and influence of chronic TAC nephrotoxicity are not fully elucidated, we studied the clinicohistological characteristics of chronic TAC nephrotoxicity in kidney transplants. PATIENTS AND METHODS: We retrospectively studied the clinicohistological profiles of 15 transplant patients under TAC-based immunosuppression, who were diagnosed as chronic TAC nephrotoxicity by allograft biopsies, showing characteristic arteriolopathy--periodic acid-Schiff PAS--positive hyaline thickening in small arteries--between January 2004 and December 2005. The mean recipient age was 37.3 years and they consisted of 11 men and 4 women. The mean age of their donors was 59.4 years. RESULTS: The diagnoses of chronic TAC nephrotoxicities were established at an average of 54.7 months postoperatively. The severities of arteriolopathy were moderate in eight cases and severe in eight cases. The mean dosage of TAC at the time of diagnoses was 0.054 mg/kg with mean whole blood trough levels of 5.09 ng/mL, which is recognized to be within the so-called recommended level. Moderate to severe arteriosclerosis of medium-sized arteries were observed in 12 cases (80.0%). CONCLUSION: The existence of moderate to severe arteriosclerosis in medium-sized arteries would have the potential of causing chronic TAC nephrotoxicities, rather than the dosage or whole blood trough level of TAC.

Continent orthotopic ileal neobladder after kidney transplantation in a patient with urothelial cell carcinoma associated with Chinese herb nephropathy.

A 58-year-old man underwent kidney transplantation on November 14, 2002 for end-stage kidney disease after Chinese herb nephropathy. Immunosuppressive therapy was maintained with tacrolimus, mycophenolate mofetil, and methylpredonisolone. He was diagnosed with right ureteral cancer and underwent right nephroureterectomy on December 13, 2003. Then, he underwent left nephroureterectomy for left ureteral cancer on March 5, 2004. Subsequently, he was diagnosed with multiple bladder cancers and carcinoma in situ. On August 31, he underwent radical cystectomy with an orthotopic ileal neobladder (Studer's method). The postoperative course was uneventful. After 3 years follow-up, this patient shows no evidence of recurrence and his serum creatinine level is stable (1.7 mg/dL). The continence is maintained during both day and night; he voids without intermittent self-catheterization. We suggest that an orthotopic ileal neobladder is a safe method of urinary diversion after cystectomy in kidney transplant recipients.

Omega filter installed in the 1MV microscope of Kyushu University.

A 1.25MV high-voltage electron microscope with a B-type omega filter has been successfully installed at Kyushu University. An image detection chamber has been set inside a concrete block below the ground level without changing the frame structure for anti-vibration. Nearly the same design as that for the 200kV microscope has been kept for the present omega filter except for its size. A new pre- and post-filter lens system with rotation-free imaging has been designed. Energy resolution, beam shape and stability of the filter have been measured. Some application data have been obtained to demonstrate the performance of the filter.

Analysis of renal transplant protocol biopsies in ABO-incompatible kidney transplantation.

Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.

[Prognosis for the cases after resection of pulmonary metastasis of osteosarcoma].

Osteosarcoma commonly metastasize to the lungs. Sixty-six cases with surgical treatment for pulmonary metastasis of osteosarcomas have been experienced for past 25 years in our hospital. Disease free interval (DFI) and the number of metastatic lesions were assessed in relation to their prognosis. As a result of our assessment, fewer metastasis (3 or less), and longer DFI (1 year or more) had relations to longer post-thoracotomy survival. And the relations between the number of metastatic lesions and DFI were found. Fewer metastasis were associated with longer DFI, and multiple metastasis were associated with short DFI. The cases with fewer metastasis (3 or less) and longer DFI (1 year or more) might have a survival advantage.